DC-SIGN Binding Contributed by an Extra N-Linked Glycosylation on Japanese Encephalitis Virus Envelope Protein Reduces the Ability of Viral Brain Invasion
The major structural envelope (E) protein of Japanese encephalitis virus (JEV) facilitates cellular binding/entry and is the primary target of neutralizing antibodies. JEV E protein has one N-linked glycosylation site at N154 (G2 site), but the related dengue virus E protein has two glycosylation si...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2018-07-01
|
| Series: | Frontiers in Cellular and Infection Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fcimb.2018.00239/full |
| _version_ | 1818304935750533120 |
|---|---|
| author | Jian-Jong Liang Min-Wei Chou Yi-Ling Lin Yi-Ling Lin |
| author_facet | Jian-Jong Liang Min-Wei Chou Yi-Ling Lin Yi-Ling Lin |
| author_sort | Jian-Jong Liang |
| collection | DOAJ |
| description | The major structural envelope (E) protein of Japanese encephalitis virus (JEV) facilitates cellular binding/entry and is the primary target of neutralizing antibodies. JEV E protein has one N-linked glycosylation site at N154 (G2 site), but the related dengue virus E protein has two glycosylation sites at N67 (G1 site) and N153 (G2 site). We generated three recombinant JEVs with different glycosylation patterns on the E protein. As compared with wild-type (WT) JEV with G2 glycosylation, viral growth in culture cells as well as neurovirulence and neuroinvasiveness in challenged mice were reduced when infected with the G1 mutant (E-D67N/N154A) with glycosylation shifted to G1 site, and the G0 mutant (E-N154A) with non-glycosylation. The G1G2 mutant (E-D67N), with E-glycosylation on both G1 and G2 sites, showed potent in vitro viral replication and in vivo neurovirulence, but reduced neuroinvasiveness. Furthermore, the JEV mutants with G1 glycosylation showed enhanced DC-SIGN binding, which may then lead to reduced brain invasion and explain the reason why WT JEV is devoid of this G1 site of glycosylation. Overall, the patterns of N-linked glycosylation on JEV E proteins may affect viral interaction with cellular lectins and contribute to viral replication and pathogenesis. |
| first_indexed | 2024-12-13T06:18:36Z |
| format | Article |
| id | doaj.art-9f5cd239e1234f22a42c86c52a82f6b6 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-12-13T06:18:36Z |
| publishDate | 2018-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-9f5cd239e1234f22a42c86c52a82f6b62022-12-21T23:56:54ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882018-07-01810.3389/fcimb.2018.00239388501DC-SIGN Binding Contributed by an Extra N-Linked Glycosylation on Japanese Encephalitis Virus Envelope Protein Reduces the Ability of Viral Brain InvasionJian-Jong Liang0Min-Wei Chou1Yi-Ling Lin2Yi-Ling Lin3Institute of Biomedical Sciences, Academia Sinica, Taipei, TaiwanInstitute of Biomedical Sciences, Academia Sinica, Taipei, TaiwanInstitute of Biomedical Sciences, Academia Sinica, Taipei, TaiwanGenomics Research Center, Academia Sinica, Taipei, TaiwanThe major structural envelope (E) protein of Japanese encephalitis virus (JEV) facilitates cellular binding/entry and is the primary target of neutralizing antibodies. JEV E protein has one N-linked glycosylation site at N154 (G2 site), but the related dengue virus E protein has two glycosylation sites at N67 (G1 site) and N153 (G2 site). We generated three recombinant JEVs with different glycosylation patterns on the E protein. As compared with wild-type (WT) JEV with G2 glycosylation, viral growth in culture cells as well as neurovirulence and neuroinvasiveness in challenged mice were reduced when infected with the G1 mutant (E-D67N/N154A) with glycosylation shifted to G1 site, and the G0 mutant (E-N154A) with non-glycosylation. The G1G2 mutant (E-D67N), with E-glycosylation on both G1 and G2 sites, showed potent in vitro viral replication and in vivo neurovirulence, but reduced neuroinvasiveness. Furthermore, the JEV mutants with G1 glycosylation showed enhanced DC-SIGN binding, which may then lead to reduced brain invasion and explain the reason why WT JEV is devoid of this G1 site of glycosylation. Overall, the patterns of N-linked glycosylation on JEV E proteins may affect viral interaction with cellular lectins and contribute to viral replication and pathogenesis.https://www.frontiersin.org/article/10.3389/fcimb.2018.00239/fullJapanese encephalitis virusenvelope proteinglycosylationvaccine potentialDC-SIGN |
| spellingShingle | Jian-Jong Liang Min-Wei Chou Yi-Ling Lin Yi-Ling Lin DC-SIGN Binding Contributed by an Extra N-Linked Glycosylation on Japanese Encephalitis Virus Envelope Protein Reduces the Ability of Viral Brain Invasion Frontiers in Cellular and Infection Microbiology Japanese encephalitis virus envelope protein glycosylation vaccine potential DC-SIGN |
| title | DC-SIGN Binding Contributed by an Extra N-Linked Glycosylation on Japanese Encephalitis Virus Envelope Protein Reduces the Ability of Viral Brain Invasion |
| title_full | DC-SIGN Binding Contributed by an Extra N-Linked Glycosylation on Japanese Encephalitis Virus Envelope Protein Reduces the Ability of Viral Brain Invasion |
| title_fullStr | DC-SIGN Binding Contributed by an Extra N-Linked Glycosylation on Japanese Encephalitis Virus Envelope Protein Reduces the Ability of Viral Brain Invasion |
| title_full_unstemmed | DC-SIGN Binding Contributed by an Extra N-Linked Glycosylation on Japanese Encephalitis Virus Envelope Protein Reduces the Ability of Viral Brain Invasion |
| title_short | DC-SIGN Binding Contributed by an Extra N-Linked Glycosylation on Japanese Encephalitis Virus Envelope Protein Reduces the Ability of Viral Brain Invasion |
| title_sort | dc sign binding contributed by an extra n linked glycosylation on japanese encephalitis virus envelope protein reduces the ability of viral brain invasion |
| topic | Japanese encephalitis virus envelope protein glycosylation vaccine potential DC-SIGN |
| url | https://www.frontiersin.org/article/10.3389/fcimb.2018.00239/full |
| work_keys_str_mv | AT jianjongliang dcsignbindingcontributedbyanextranlinkedglycosylationonjapaneseencephalitisvirusenvelopeproteinreducestheabilityofviralbraininvasion AT minweichou dcsignbindingcontributedbyanextranlinkedglycosylationonjapaneseencephalitisvirusenvelopeproteinreducestheabilityofviralbraininvasion AT yilinglin dcsignbindingcontributedbyanextranlinkedglycosylationonjapaneseencephalitisvirusenvelopeproteinreducestheabilityofviralbraininvasion AT yilinglin dcsignbindingcontributedbyanextranlinkedglycosylationonjapaneseencephalitisvirusenvelopeproteinreducestheabilityofviralbraininvasion |